350 adult smokers will be enrolled in the study. Primary aim: To conduct the first randomized controlled trial of the efficacy of selegiline patch (STS) for the treatment of nicotine dependence. We propose that STS will promote more durable treatment effects by alleviating craving and other withdrawal symptoms that emerge following nicotine deprivation and have the effect of promoting relapse. Our primary hypothesis is that smokers randomized to receive STS will have a higher prolonged abstinence rate (PA) at 6-month follow-up than those who receive matching placebo. PA at 6 months will be the outcome measure used to evaluate the primary hypothesis. PA is defined as a report of non-smoking following an initial 2-week grace period during which any smoking is not counted as a failure and an expired-air carbon monoxide level of <9PPM. With 175 participants per cell we will have at least 80 percent power at alpha of .05 to detect a difference in abstinence rates of at least 10 -15 percent across a range of success probabilities. Secondary obiectives: we propose to genotype all subjects for polymorphisms at loci hypothesized to affect nicotine dependence and/or selegiline efficacy. These include the serotonin transporter, the dopamine transporter, dopamine D2 receptor, and the dopamine Dpercent receptor. Analyses will examine whether polymorphisms at these loci moderate response to treatment. The proposed study will address several important gaps in our knowledge of effective smoking cessation treatment. First, this will be the first RCT to examine the efficacy of selegiline patch for the treatment of nicotine dependence. Second, this study will be one of the first, if not the first, prospective trial of smoking cessation techniques in which genetic data are included as predictors of outcome. Third, we plan to conduct mediation and moderation analyses to explore factors that may influence response to treatment. The study will provide important practical information to the medical and health communities concerning the utility of selegiline for smoking cessation and will advance our knowledge of the underlying relationship of nicotine addiction and depression.